Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib 10 mg twice daily (BID) improved quality of life (QoL) in two Phase 3 induction studies of patients with moderately to severely active UC (OCTAVE Induction 1 & 2) .
Methods: OCTAVE Sustain (NCT01458574) was a Phase 3, randomised, double-blind, placebo-controlled study that enrolled patients who completed OCTAVE Induction 1 or 2 with clinical response (≥3 points and ≥30% decrease from baseline (BL) Mayo score plus decrease in rectal bleeding subscore of ≥1 or rectal bleeding subscore ≤1). Patients were re-randomised (1:1:1) to placebo, tofacitinib 5 or 10 mg BID for 52 weeks. QoL was assessed at Weeks 24 and 52 using the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ) and the Short Form-36 (SF-36; version 2, 1-week recall; 8 domain scores summarised as Physical and Mental Component Summaries [PCS and MCS]). Clinically relevant endpoints including IBDQ Remission (IBDQ Score ≥170) and Response (≥16-point improvement from induction study BL IBDQ Score), were compared by Cochran-Mantel-Haenszel chi-square test. Continuous endpoints were analysed using a linear mixed-effects model.
Results: OCTAVE Sustain randomised 593 patients (placebo: n=198; 5 mg BID: n=198; 10 mg BID: n=197). At Sustain BL, across treatment groups, mean IBDQ total score ranged from 166.7–167.7, and mean SF-36 PCS and MCS ranged from 49.3–50.5 and 47.8–49.0, respectively. IBDQ and SF-36 endpoints at Weeks 24 and 52 are shown in Table 1. There was no significant change from Sustain BL in total IBDQ scores at Weeks 24 and 52 with tofacitinib (Table 1). In contrast, IBDQ total score decreased with placebo (p<0.001 for all comparisons of tofacitinib vs placebo). Significantly more patients achieved IBDQ remission and response with both tofacitinib doses vs placebo at all time points (p<0.001 for all comparisons). Mean changes from Sustain BL in SF-36 PCS and MCS and all individual domain scores showed similar benefit with both tofacitinib doses vs placebo at Weeks 24 and 52 (p<0.001 for all comparisons).
Conclusions: For patients with moderate to severe UC and clinical response to tofacitinib induction therapy, significant and clinically meaningful improvements in QoL (assessed by IBDQ and SF-36) were maintained with tofacitinib 5 and 10 mg BID vs placebo through 52 weeks of maintenance therapy.
 Panés J et al, (2016), Improvement in patient-reported outcomes in 2 Phase 3 studies of tofacitinib in patients with moderately to severely active ulcerative colitis, J Crohns Colitis, 10: S283