Improvements in disease activity partially mediate the effect of tofacitinib treatment on generic and disease-specific health-related quality of life in patients with ulcerative colitis: data from the OCTAVE program

Background: Patients with ulcerative colitis (UC) often report impaired health-related quality of life (HRQoL). Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of UC. In addition to previous demonstrations of improved clinical measures (e.g., Mayo score), tofacitinib has been shown to improve HRQoL in patients with UC. This analysis explored the interrelationships among tofacitinib treatment, HRQoL, and disease activity (measured using Mayo subscores) using mediation modeling. Methods: Data were collected from two 8-week induction studies (OCTAVE Induction 1 and 2) in patients with moderate to severe UC treated with tofacitinib or placebo. Two mediation models were specified. First, Mayo subscores were mediators between the binary treatment variable (tofacitinib vs placebo) and the eight Short Form-36 Health Survey (SF 36) domain scores as outcomes. Second, the four Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores served as outcomes. Both models used data collected at Week 8. Results: Overall, 1073 and 1079 patients were included in the SF-36- and IBDQ-based models, respectively. For all SF-36 domains, improvements in Mayo subscores were estimated to explain 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p<0.05). For all IBDQ domains, improvements in Mayo subscores explained 71.6% (systemic symptoms) to 84.7% (emotional function) of the total treatment effect (all p<0.05). Conclusion: Mayo scores and Mayo subscores are significant but incomplete contributors to tofacitinib's effect on HRQoL in patients with moderate to severe UC. ClinicalTrials.gov: NCT01465763; NCT01458951.