S798 Indirect Effects of Tofacitinib on Work Productivity in Patients with Ulcerative Colitis: A Mediation Analysis Between Work Productivity and the Inflammatory Bowel Disease Questionnaire

Abstract

Introduction: Tofacitinib is an oral small molecule JAK inhibitor for the treatment of UC. Tofacitinib induction treatment has been shown to improve work productivity in patients (pts) with UC. However, it is unknown whether improvements in work productivity are fully explained by changes in the Inflammatory Bowel Disease Questionnaire (IBDQ) or if other factors not captured by these changes contribute. Methods: We evaluated the interrelationship between IBDQ domains (bowel, emotional, social, and systemic) and Work Productivity and Activity Impairment-UC (WPAI-UC) components (overall work productivity loss and activity impairment) among pts in the Phase 3, 8-week induction studies that evaluated tofacitinib as induction therapy for UC (OCTAVE Induction 1&2; NCT01465763; NCT01458951). A mediation model used IBDQ domains as mediators of the treatment effect on WPAI-UC components as outcomes. Work productivity loss and activity impairment can be viewed as complementary outcomes covering work and other daily activities, respectively. Analyses used all available pooled data from Week 8 in pts receiving tofacitinib/placebo. Results: There were 490 and 1,083 pts available for analysis in the models assessing work productivity loss and activity impairment, respectively. For the models evaluating work productivity loss (Figure a) and activity impairment (Figure b), the effects of tofacitinib were fully mediated via IBDQ domains; the largest effects were via the IBDQ social domain, which represented 57.4% and 58.4% of the effects of tofacitinib on work productivity loss and activity impairment, respectively (Figure a and Figure b, respectively). The impact of tofacitinib via the IBDQ emotional domain did not affect work productivity loss or activity impairment. Conclusion: This analysis suggests that the effects of tofacitinib induction therapy on work productivity loss and activity impairment in pts with UC were fully mediated via IBDQ bowel, social, and systemic domains. These findings provide insights into the interrelationship between IBDQ domains and WPAI-UC and may help inform healthcare providers on the impact of UC therapies on pts' work and leisure activities.Figure 1.: Summary of indirect (mediated through IBDQ domains) effects of tofacitinib vs placebo on the a) work productivity loss and b) activity impairment WPAI-UC components as a percentage of the total treatment effect. The WPAI-UC is a self-administered six-item questionnaire that generates four metrics: absenteeism (work time missed), presenteeism (impairment whilst working), productivity loss (overall work impairment from the combination of absenteeism and presenteeism), and activity impairment (non-work activity impairment). WPAI-UC component scores are expressed as percentages, with a higher percentage indicating greater impairment and less productivity. The IBDQ evaluates disease-related quality of life by 32 items over four domains: bowel (total domain score ranges from 10 to 70), emotional (total domain score ranges from 12 to 84), social (total domain score ranges from 5 to 35), and systemic (total domain score ranges from 5 to 35). For the total score (ranges from 32 to 224) and each domain, a higher score indicates a better quality of life. IBDQ, Inflammatory Bowel Disease Questionnaire; WPAI-UC, Work Productivity and Activity Impairment-Ulcerative Colitis