P370 A randomised controlled trial of acceptance and commitment therapy for the treatment of stress in inflammatory bowel disease

Abstract

S266 Poster presentations mod (n=6) or placebo (n=2), starting at 0.1mg. Following screening (21 days), single doses were administered on Day 1 and observations undertaken until at least Day 7. In Study 002, up to 12 subjects in each of 3 cohorts (0.7, 1.35 and 2.0mg) received etrasimod (n=10) or placebo (n=2) for 21 days. Dosing in Cohorts 4 and 5 started at 0.35 and 0.5mg for 7 days with titration to 2.0 and 3.0mg, respectively. Results: In single doses, etrasimod was well tolerated at 0.1, 0.35, 1 and 3mg. Mild-to-moderate headache (1/6-3/6 of subjects) and contact dermatitis (1/6-2/6) were the most commonly reported AEs, occurring with similar/lower frequency to placebo (2/3 each). In the 5mg cohort, 4 events of first or second degree AV block, with and without bradycardia, occurred in 3/6 subjects; although asymp-tomatic, further dose escalation was stopped. Dose-related declines in blood pressure and heart rate from baseline (vs placebo) were statistically significant with 3.0 and 5.0mg doses only (p<0.05); all resolved without intervention. With multiple dosing, common AEs with etrasimod versus placebo included contact dermatitis (1/10-7/10 of subjects vs. 6/10), constipation (2/10-3/10% vs. 0), headache (1/10-3/10% vs. 4/10) and diarrhoea (2/10-3/10% vs. 1/10). These were mild-to-moderate, and not dose related. Small asymptomatic declines in blood pressure and heart rate were noted. 3 subjects developed first degree AV block (placebo: 1; 2mg: 1; 0.5/3mg: 1). No serious AEs or deaths were reported. Single etrasimod doses of 3mg and 5mg decreased total peripheral blood lymphocyte counts to 52.5% and 35.9% of baseline and with time to nadir of ∼15 hours and ∼11 hours post-dose, respectively. With multiple dosing, etrasimod had a dose-dependent effect on lymphocyte lowering, plateauing at 2mg QD. Median reduction in lymphocyte counts was ∼67% for the higher doses (2 and 3mg QD for 21 days). For both studies, mean counts returned to baseline levels within 7 days of dosing discontin-uation. Conclusions: In Phase I studies, etrasimod was well tolerated and modulated lymphocyte levels when administered orally at dose levels ≤3mg in healthy volunteers. These findings support further evaluation of this S1P modulator in clinical studies. Background: The inflammatory bowel diseases are associated with high levels of psychological stress. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures along with commitment and behaviour-change strategies to increase psychological flexibility and reduce stress. The aim of this study was to determine the effect of ACT on stress in IBD patients. Methods: Ninety five patients (mean age 40 years; 42 male) with quiescent or mildly active IBD were randomly assigned to an eight week ACT course (n=47) or to a control group (n=48) stratified by disease type and gender. Clinical, demographic, disease activity, biochemical (including CRP and faecal calprotectin) and psychological data were collected at i) baseline, ii) post-intervention (8 weeks) and iii) 20 weeks. Patients on antidepressants, those with psychiatric disorders or those who had received steroids over the previous three