P369 Improvement in patient-reported outcomes in 2 Phase 3 studies of tofacitinib in patients with moderately to severely active ulcerative colitis
J. Panés*1, C. Su2, A. Marren2, D. Yu2, D. Woodworth2, H. Zhang2, P. Healey3
1Hospital Clinicas de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, 2Pfizer Inc, Collegeville, United States, 3Pfizer Inc, Groton, United States
Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Two Phase 3 randomised placebo-controlled studies (OCTAVE Induction 1, NCT01465763; OCTAVE Induction 2, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs placebo as induction therapy for patients with moderate-to-severe UC. Here we report the effect of tofacitinib vs placebo on patient-reported outcomes (PROs) in these studies.
Patients in OCTAVE Induction 1 and OCTAVE Induction 2 were randomised (4:1) to receive treatment with tofacitinib 10 mg or placebo BID for 8 weeks. Patients were ≥18 years old with moderately to severely active UC defined at baseline by: Mayo score of ≥6; rectal bleeding sub-score ≥ 1 and an endoscopic sub-score ≥ 2. Patients had previous failure or intolerance to treatment with ≥1 of: corticosteroids, azathioprine or 6-mercaptopurine, or tumour necrosis factor inhibitors. PRO endpoints included Inflammatory Bowel Disease Questionnaire (IBDQ at Weeks 4 and 8; including the proportions of patients with IBDQ total score ≥ 170 [IBDQ Remission], and ≥16-point increase from baseline IBDQ [IBDQ Response]), and Short Form-36 (SF-36) Physical and Mental Component scores at week 8. Statistical methods for comparing tofacitinib vs placebo were: a linear mixed effect model for changes from baseline in IBDQ total score; Cochran–Mantel–Haenszel Chi-square test for binary endpoints based on IBDQ; and analysis of covariance for SF-36 summary scores.
In the study, 598 patients were treated in OCTAVE Induction 1 (tofacitinib 10 mg BID: n = 476; placebo: n = 122) and 541 in OCTAVE Induction 2 (10 mg BID n = 429; placebo n = 112). Mean baseline IBDQ total (OCTAVE Induction 1, 10 mg BID, 126.0; placebo, 127.0; OCTAVE Induction 2, 10 mg BID, 123.7; placebo, 120.1) indicated substantial patient-reported burden of disease. In both studies, tofacitinib treatment resulted in improvements in PRO endpoints at week 8, with statistically significant differences vs placebo in IBDQ total score, IBDQ Remission, IBDQ Response, and SF-36 Physical and Mental Component scores (Table 1). Statistically significant differences vs placebo were also seen in IBDQ total score, IBDQ Remission and IBDQ Response at week 4 in both studies (Table 1).
In patients with moderate-to-severe UC, tofacitinib significantly improved quality of life across multiple PROs compared with placebo. A significant benefit was observed as early as week 4 (first post-baseline assessment) for IBDQ.
Table 1. Summary of PRO endpoints in OCTAVE Induction 1 and OCTAVE Induction 2