Introduction

Ulcerative colitis exerts a significant disease burden and hence restoration or normalization of health-related quality of life (HRQoL) is an important goal. Tofacitinib, an oral small-molecule JAK inhibitor, statistically significantly improved Mayo score-based outcomes, as well as Short Form-36 Health Survey (SF-36) and Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores, versus placebo. It is unclear whether its effects on HRQoL are fully explained by changes in disease activity or if there are other mediators of treatment. 

Aim

To determine (1) whether tofacitinib treatment directly contributes to all changes in SF-36 and IBDQ domain scores in patients with UC outside of any changes in Mayo subscores, (2) whether changes in SF-36 and IBDQ domain scores are merely a consequence of Mayo subscore changes, or (3) whether changes in SF-36 and IBDQ domain scores are the result of a combination thereof.

Patient Profile

• 1,161 moderate to severe UC patients who had previously experienced treatment failure on, or intolerance to, corticosteroids, azathioprine, mercaptopurine, adalimumab, or infliximab

Method

Study Design

• Randomized, double-blind, placebo-controlled, identically designed 8-week induction studies of tofacitinib (OCTAVE Induction 1 & 2)
• Patients were randomized to receive tofacitinib 10 mg BID or placebo.

Endpoints

• Short Form-36 Health Survey (SF-36) domain scores (Mayo subscores were mediators between treatment, tofacitinib/placebo, and SF-36)

• Inflammatory Bowel Disease Questionnaire (IBDQ) domain scores

Results

Efficacy

• Tofacitinib directly improved the outcomes of bodily pain, role-physical, and vitality in the SF-36 domains
• Improvements in Mayo scores and subscores explained 65.6% (bodily pain) to 92.9% (mental health) of the total treatment effect on SF-36 domain scores (all p<0.05)
• Tofacitinib directly improved disease-specific HRQoL parameters of bowel symptoms, systemic symptoms and social function) in the IBDQ domains. This was outside the benefit of improving stool frequency, rectal bleeding, endoscopic appearance or Physician Global Assessment, as measured by the Mayo score.
• For all IBDQ domains, significant improvement in Mayo scores and subscores explained 71.6% (systemic symptoms) to 84.7% (emotional function) of the total treatment effect (all p<0.05)

Figure 1: Effect of Tofacitinib versus placebo on SF-36 and IBDQ domains, as a percentage of the total treatment effect

Conclusion

• Mayo score and its subscores are significant but incomplete contributors to tofacitinib's effect on HRQoL in patients with moderate to severe UC.
• These results reinforce the value of clinicians using patient-reported HRQoL measures in addition to Mayo score and subscores, when assessing treatment outcomes in patients with UC.