Post HOC Analysis of the Impact of Ustekinumab Treatment on Specific Items of the Inflammatory Bowel Disease Questionnaire in the Uniti-1 & 2 Programs

Background: Previous analysis of the UNITI- I & 2 and IM-UNITI phase 3 trials have shown that ustekinumab (UST) treatment improves general health status and IBD-specific HRQOL in patients with moderate to severe Crohn's disease (CD) both as intravenous (IV) induction therapy as well as subcutaneous (SC) maintenance. We conducted a post-hoc analysis to assess which items of the disease related inflammatory bowel disease questionnaire (IBDQ) had the greatest impact on health-related quality of life (HRQOL) at baseline and the effect of UST on improving these items after induction therapy. Methods: Patients with moderately to severely active CD [defined by a CD Activity Index (CDAI) of 220-450) who had inadequate response or intolerance to TNF antagonists (UNITI-1, N=741) or to conventional therapy (UNITI-2, N=627) were randomized 1:1:1 to receive UST ~6mg/kg, UST 130mg or placebo (PBO) intravenously (IV) at week 0 and the IBDQ score was assessed at baseline and week 8. In this post-hoc analysis, items of the IBDQ with the greatest impact on HRQOL at baseline were defined as having a pooled mean score <3.5 [(scale 1 (worse) - 7 (better)] at baseline and were selected for the analysis. Changes in mean scores were measured at week 8 (UNITI-1&2) and compared to placebo. Results: At baseline of UNITI-1&2, 11 of 32 items in the IBDQ had mean scores <3.5 and were determined as having a marked impact on quality of life: loose stools, feeling relaxed, fatigue, feeling unwell, abdominal pain, energy, sleep, abdominal cramps, happy with life, leisure activities, and feeling frustrated (Table 1). By week 8 statistically significant improvements were seen for the majority of these items in the UST 130mg arm vs placebo and for all items in the ~6mg/Kg vs placebo in UNITI-1& 2 (Table 2.a-c). Moreover, greater improvements were seen in the TNF-antagonist naïve population of UNITI-2 which were all statistically significant in the ~6mg/Kg UST arm vs placebo. Conclusion: Specific items in the IDBQ including fatigue, sleep, loose stools, and items relating to emotional/social such as feeling unwell and impact on leisure activities had the greatest negative impact on QoL at baseline. A single IV induction dose of UST treatment significantly improved the mean scores in these QoL items in patients with moderate to severe CD patients. [Table Presented]