P252 Measuring the mediating effects of Mayo score components for tofacitinib on disease-specific quality of life in ulcerative colitis: data from the OCTAVE programme

Abstract

BACKGROUND: Composite efficacy endpoints in ulcerative colitis (UC) clinical trials are typically based on the Mayo score (MS), which includes 4 components: stool frequency, rectal bleeding, endoscopic appearance, and physician assessment. Although disease specific quality of life (QoL) measures like the Inflammatory Bowel Disease Questionnaire (IBDQ) are also frequently included, it is unclear whether treatment effects on QoL are fully explained by MS changes or if there are other unobserved variables in play. The current study explored the interrelationship among treatment, IBDQ scores, and MS components using a mediation modeling framework. METHOD(S): Pooled data at the end (week 8) of the two double-blind, identically designed induction studies of tofacitinib (OCTAVE Induction 1 & 2, NCT01465763 & NCT01458951) were used. Tofacitinib is an oral, small molecule Janus kinase inhibitor approved in several countries for the treatment of ulcerative colitis (UC). A mediation model was specified such that the MS components served as the mediators between treatments (active treatment vs. placebo) and IBDQ domain scores (bowel symptoms, systemic symptoms, emotional functioning, and social functioning). Our primary interest was the extent to which treatment affects the IBDQ domains outside of any change in MS components (i.e., the direct path). RESULT(S): 1079 patients with moderately to severely active UC at baseline were included. Majority of treatment effect on the IBDQ was mediated by MS components. For all IBDQ domains, the indirect path (i.e., the pathway from treatment to MS component and then to each IBDQ domain score) was significant (all p