Association between Duration of Latest Flare before Induction Treatment with Tofacitinib and Efficacy Outcomes in Patients with Ulcerative Colitis

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. The duration of active disease prior to starting treatment may impact treatment effects. We evaluated the association between duration of the latest flare before starting tofacitinib therapy and efficacy outcomes in the tofacitinib UC clinical program.

METHODS:

Patients (pts) received tofacitinib 10 mg twice daily (BID) or placebo in OCTAVE Induction 1&2 (NCT01465763; NCT01458951) and responders received tofacitinib 5 or 10 mg BID or placebo during OCTAVE Sustain (final efficacy assessment at Wk52; NCT01458574). Pts were stratified by UC flare duration (ie duration of active disease; <3 and ≥3 mo) prior to enrollment in OCTAVE Induction 1&2. Differences between the change from baseline Mayo stool frequency subscore (SF), Mayo rectal bleeding subscore (RB), and partial Mayo score (PMS) at Wk2 of OCTAVE Induction 1&2 between flare duration groups were assessed using ANOVA. Associations between flare duration and efficacy endpoints were assessed using the Cochran-Mantel-Haenszel chi-squared test.

RESULTS:

Among the 905 pts who received tofacitinib 10 mg BID in OCTAVE Induction 1&2, 443 and 462 pts had flare durations of <3 and ≥3 mo, respectively. A higher proportion of pts with ≥3 mo flare duration had pancolitis (53.7%) vs pts with <3 mo flare duration (48.8%); this was also true for prior TNFi failure (60% vs 42%). Mean baseline total Mayo score in both groups was 9.0. In OCTAVE Induction 1&2, a numerically higher proportion of pts with <3 mo flare duration met efficacy endpoints vs pts with ≥3 mo, with a significant association. Changes from baseline SF, RB, and PMS at Wk2 were significantly greater in pts with <3 vs ≥3 mo flare duration. Among pts who received tofacitinib 5 mg BID in OCTAVE Sustain, a numerically higher proportion with <3 mo flare duration met efficacy endpoints at Wk52 vs pts with ≥3 mo; similar proportions of tofacitinib 10 mg BID-treated pts across flare duration groups met efficacy endpoints (Table).

CONCLUSION:

These post hoc analyses showed that latest flare duration was significantly associated with the efficacy of tofacitinib 10 mg BID induction therapy at Wk8, with shorter duration (,3 mo) associated with greater efficacy, potentially implying that a timely intervention during a new flare may, as expected, lead to a better outcome for induction. During maintenance, flare duration had less impact on efficacy, with similar responses at Wk52 between tofacitinib 10 mg BID groups.