P378 Safety of adalimumab in global clinical trials of ulcerative colitis patients

Abstract

Background:The use of objective, validated instruments to evaluate sleep impairment in Crohn's disease (CD) studies is limited. This report (1)describes the extent of sleep impairment reported in CERTIFI using the Jenkins Sleep Evaluation Questionnaire (JSEQ) and (2)establishes a clinically meaningful improvement threshold for the JSEQ. Methods:Patients with moderate-to-severe CD(CDAI ≥220 and ≤450) who had previously failed or were intolerant to ≥1TNF antagonists were randomized to placebo(PBO) or ustekinumab(UST) induction at wk0. Primary endpoint was clinical response(≥100-pt reduction in CDAI from baseline) at wk6. Sleep impairment was assessed using JSEQ(total score 0-20; higher scores indicate greater sleep impairment) at baseline and wk6. Relationships between baseline sleep impairment, clinical disease activity(CDAI), and HRQoL impact(IBDQ) were evaluated using Pearson correlation. Clinically meaningful improvement threshold of JSEQ was established with the anchor-based [clinical response by reduction in CDAI of ≥70-pt or clinically meaningful improvement (≥16-pt) in IBDQ]and distribution-based( change by one-half of the standard deviation[SD] of baseline JSEQ score) methods. Proportion of patients who achieved clinically meaningful improvements in JSEQ at wk6 was determined and compared. Results:At baseline, both groups(n=526) experienced similar degree of moderate sleep impairment, with JSEQ scores (mean±SD) of 11.0±4.30(PBO) and 11.0±4.59(UST), respectively. About 60% of patients were waking up feeling tired and worn out; and about 30-35% of patients had trouble falling asleep, staying asleep, and woke up several times during the night for 1530 days in the previous month. At baseline, JSEQ was correlated with CDAI (r= 0.19,p,0.0001) and IBDQ(r=-0.39,p,0.0001). Using the anchor-based method, patients who achieved vs didn't achieve clinically meaningful improvements in CDAI or IBDQ at wk6 compared to baseline, reported improvements (mean±SD) from baseline in JSEQ of