Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We examined the effect of tofacitinib induction treatment on Inflammatory Bowel Disease Questionnaire (IBDQ) items in adults with moderate to severe UC.

Methods: Data were pooled from the randomized, 8‑week, double-blind, phase 3 OCTAVE Induction 1 and 2 studies. The IBDQ was self-administered by patients at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life (HRQoL). Change from baseline in IBDQ items was analyzed for 10 mg of tofacitinib twice daily (BID) vs placebo using a linear mixed-effects model, with no multiplicity adjustment performed. Effect sizes were calculated. Subgroup analyses by tumor necrosis factor inhibitor (TNFi) experience were performed.

Results: Significant improvements (nominal P < 0.05) were observed in all IBDQ items with 10 mg of tofacitinib BID vs placebo at weeks 4 and 8. For the overall population, the largest treatment differences across all items were reported for "bowel movements been loose" at weeks 4 and 8, and "problem with rectal bleeding" at week 8 (mean treatment differences all 1.1; both in bowel symptoms domain). These items also showed the largest effect sizes. Treatment benefits were generally slightly numerically higher in TNFi-experienced vs TNFi-naïve patients.

Conclusions: Tofacitinib induction therapy improved all IBDQ items vs placebo in patients with UC, reflecting improvements in HRQoL, with greatest benefits reported in bowel symptoms domain items (Funded by Pfizer Inc; OCTAVE Induction 1 and OCTAVE Induction 2; ClinicalTrials.gov, NCT01465763 and NCT01458951, respectively).

Keywords: patient-reported outcomes; tofacitinib; ulcerative colitis.

© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

FIGURE 1.

Study design of OCTAVE Induction 1 and 2. Final complete efficacy assessment at week 8. Treatment continued up to week 9; n, number of patients randomized in each treatment group.

FIGURE 2.

Effect sizes of 10 mg of tofacitinib BID vs placebo for the change from baseline for each IBDQ item in the overall population (FAS, observed case). Effect sizes are the difference in least squares means for 10 mg of tofacitinib BID vs placebo, divided by the standard deviation (SD) of baseline scores (where the SD was calculated using data from both treatment groups in both studies); 0.1 = trivial, 0.2 = small, 0.5 = medium, and 0.8 = large. Effect size categorization intervals: 0–0.15, trivial; >0.15–0.35, small; >0.35–0.65, medium; and >0.65, large. Abbreviations: ES effect sizes.

FIGURE 3.

Effect sizes of 10 mg of tofacitinib BID vs placebo for the change from baseline for each IBDQ item in TNFi-naïve and TNFi-experienced patients at week 8 (FAS, observed case). Effect sizes are the difference in least squares means for 10 mg of tofacitinib BID vs placebo, divided by the standard deviation (SD) of baseline scores (where the SD was calculated using data from both treatment groups in both studies); 0.1, trivial; 0.2, small; 0.5, medium; and 0.8, large. Effect size categorization intervals: 0–0.15, trivial; >0.15–0.35, small; >0.35–0.65, medium; and >0.65, large. Abbreviations: ES, effect sizes; FAS, full analysis set.