Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes

Abstract

Background: Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose-dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC). The objective of the current study was to determine the effect of tofacitinib on patient-reported outcomes (PROs).

Methods: Eligible patients (≥18 years of age) with a diagnosis of active UC (total Mayo score of 6-12 points and moderately-to-severely active disease on sigmoidoscopy) were randomized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg, 3 mg, 10 mg, or 15 mg, or placebo twice daily (BID) for 8 weeks. PROs were assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Inflammatory Bowel Disease Patient-Reported Treatment Impact (IBD PRTI) survey.

Results: At Week 8, mean IBDQ total scores had improved relative to baseline across all five treatment groups (baseline range 123.2-134.5; Week 8 range 149.6-175.4). Improvement from baseline was significantly greater (P = 0.001) for tofacitinib 15 mg BID versus placebo. For tofacitinib 15 mg BID, most patients reported satisfaction or extreme satisfaction, definite preference for tofacitinib, and definite willingness to use tofacitinib again on the IBD PRTI at week 8. Patients achieving endoscopic remission (Mayo endoscopy score of 0) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission.

Conclusions: Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib. The results complement previously reported efficacy and safety data for the Phase II study. (NCT 00787202, November 6, 2008).

Trial registration: ClinicalTrials.gov NCT00787202.

Figures

Figure 1

Adjusted mean change from baseline (SE) in total IBDQ score at Week 8. A higher score indicates better quality of life. The ANCOVA model used treatment group as a factor and the baseline value as a covariate. The center was not included in the model. *p = 0.001 compared with placebo (analysis of covariance). BID, twice daily; IBDQ, inflammatory bowel disease questionnaire; SE, standard error.

Figure 2

IBD PRTI score frequency distributions at Week 8 (FAS). BID, twice daily; PRTI, IBD patient-reported treatment impact (version 2) questionnaire.

Figure 3

Relationship between the IBDQ total score (all patients) versus the total Mayo score (a), the Mayo partial score (b), and the Mayo endoscopic subscore (c).

Figure 4

Relationship between the components of the IBD PRTI (all patients) including patient satisfaction (a), preference (b), and willingness (c) versus the total Mayo score. IBD PRTI item scores: Patient satisfaction assessment; Extremely dissatisfied with study drug = 1, Dissatisfied with study drug = 2, Neither satisfied nor dissatisfied with study drug = 3, Satisfied with study drug = 4, Extremely satisfied with study drug = 5. Patient preference assessment; Definitely prefer study drug over prior treatment = 1, Slightly prefer study drug = 2, No preference = 3, Slightly prefer prior treatment = 4, Definitely prefer prior treatment = 5. Patient willingness assessment; Would definitely use study drug again = 1, Might use study drug again = 2, Not sure = 3, Might not use study drug again = 4, Would definitely not use study drug again = 5.

Figure 5

Relationship between the components of the IBD PRTI (all patients) including patient satisfaction (a), preference (b), and willingness (c) versus the Mayo endoscopy score. IBD PRTI item scores: Patient satisfaction assessment; Extremely dissatisfied with study drug = 1, Dissatisfied with study drug = 2, Neither satisfied nor dissatisfied with study drug = 3, Satisfied with study drug = 4, Extremely satisfied with study drug = 5. Patient preference assessment; Definitely prefer study drug over prior treatment = 1, Slightly prefer study drug = 2, No preference = 3, Slightly prefer prior treatment = 4, Definitely prefer prior treatment = 5. Patient willingness assessment; Would definitely use study drug again = 1, Might use study drug again = 2, Not sure = 3, Might not use study drug again = 4, Would definitely not use study drug again = 5.